Sex determined provides an example of the differential control of gene expression during development, culminating in a particular sexual pathway. Unlike most other developmental phenomena, the control of sexual differentiation involves a cellular mechanism which assesses the chromosome composition of the organism. Once the presence and relative ratios os sex-specific chromosomes are determined, various genes are turned on or off in implement the sexual fate designated by the chromosome compsoition. Sex determination in the nematode, Caenorhabditis elegans follows this basic scheme and will be investigated by genetic and biochemical means in an attempt to increase the understanding of the following problems: 1. Whether the gene activity of the X chromosome is carefully regulated in hermaphrodites (XX animals) and males (XO animals) to ensure the equality in expression of X-specific genes not involved in sex determination; 2. The mechanims by which the chromosome composition, i.e. the ratio of X chromosomes to autosomes, is assessed; 3. Jpw X-specific meiotic nondisjunction--the process that results in the formation of males--is controlled; 4. Identification of the gene product and mode of action of a locus essential in sex determination. The fundamental approaches are the isolation and characterization of mutants which affect these processes in sex determination and the derivation of recombinant DNA clones which contain either X-specific DNA sequences or a locus involved in hermaphrodite sex determination. The health relatedness of this project derives from its contribution to the understanding of basic cellular control mechanisms used in higher organisms and perhaps man.